Crystalline silica (CS) particle exposure leads to silicosis which is characterized as progressive fibrosis. Fibroblasts are vital effector cells in fibrogenesis. Emerging studies have identified immune sentinel roles for fibroblasts in chronic disease, while their immune-modulatory roles in silicosis remain unclear. Herein, we show that group 2 innate lymphoid cell (ILC2) conversion to ILC1s is closely involved in silicosis progression, which is mediated by activated fibroblasts via interleukin (IL)-18. Mechanistically, Notch3 signaling in mechanics-activated fibroblasts modulates IL-18 production via caspase 1 activity. The mouse-specific Notch3 knockout in fibroblasts retards pulmonary fibrosis progression that is linked to attenuated ILC conversion. Our results indicate that activated fibroblasts in silicotic lungs are regulators of ILC2-ILC1 conversion, associated with silicosis progression via the Notch3-IL-18 signaling axis. This finding broadens our understanding of immune-modulatory mechanisms in silicosis, and indicates potential therapeutic targets for lung fibrotic diseases.
The utilization of sulfide-based solid electrolytes represents an attractive avenue for high safety and energy density all-solid-state batteries. However, the potential has been impeded by electrochemical and mechanical stability at the interface of oxide cathodes. Plastic crystals, a class of organic materials exhibiting remarkable elasticity, chemical stability, and ionic conductivity, have previously been underutilized due to their susceptibility to dissolution in liquid electrolytes. Nevertheless, their application in all-solid-state batteries presents a paradigm that could potentially overcome longstanding interface-related obstacles. This study presents a facile approach to enhancing the performance of sulfide-based solid-state batteries by utilizing nickel-rich oxide cathodes coated with ionically conductive plastic crystals. For employing plastically deformed succinonitrile as a metal ion ligand, it simultaneously supports mechanical stability and interfacial conduction, while LiDFOB establishes moderate ionic conductivity and a stable cathode electrolyte interphase (CEI). The synergistic effects of these mechanisms culminate in remarkable long-term performance metrics, with the capacity retaining 80% after 1529 cycles. Furthermore, this stability is maintained even when the areal capacity density is increased to a substantial 3.53 mA h cm–2. By combining electrochemical stability with mechanical plasticity, this approach opens possibilities for the development of long-lasting solid-state batteries suitable for practical applications.
Abstract Exposure to crystalline silica particle leads to silicosis characterized as progressive fibrosis. Fibroblasts are described as vital effector cells in fibrogenesis. Emerging studies identified immune sentinel role of fibroblasts in chronic disease, while their immune-modulatory role in silicosis remained elusive. Herein, we confirmed that a conversion of ILC2 to ILC1 closely involved in silicosis was mediated by activated fibroblast via IL-18. Mechanistically, Notch3 signaling in mechanics-activated fibroblasts modulated IL-18 production. The mice specific knockout Notch3 in fibroblast exerted retardatory progression of pulmonary fibrosis that tightly linked to attenuated conversion of ILCs. Our results indicated that the activated-fibroblast in silicotic lung served as a regulator of ILC2-ILC1 conversion that associated with silicosis progression via Notch3-IL-18 axis. The findings broadened the cognitive boundaries of the immune regulation of silicosis, also provide potential therapeutic targets in treating lung fibrotic diseases.
Background: Occupational crystalline silica (CS) particle exposure leads to silicosis. The burden of CS-associated disease remains high, and treatment options are limited due to vague mechanisms. CD4 tissue-resident memory T cells (T ) accumulate in the lung responded to CS particles, mediating the pathogenesis of silicosis. Methods: Based on silicosis murine model by single intratracheal instillation of CS suspension, we further employ adoptive transfer, FTY720 treatment, and parabiosis murine model to explore their source. After defining T cell subsets by CD103 and CD69, we intervene CD103 subset and block IL-7 signaling to alleviate silicosis. Results: The CD4 T cells are derived from peripheral lymphocyte recruitment and in situ expansion. Specifically, T -Treg cells depend more on circulating T cell replenishment. The cell retention markers CD103 and CD69 can divide the T cells into effector and regulatory subsets. However, targeting CD103 T -Treg cells do not mitigate disease phenotype since the T subsets exerted immunosuppressive but not pro-fibrotic roles. We further dissect that IL-7 signaling promotes the progression of silicosis by tuning the maintenance of T -effector T cells. Conclusion: Our findings highlight the distinct role of CD4 T cells in mediating CS-induced fibrosis and provide potential therapeutic strategies for silicosis.
Triple structural factors, including sophorose affinity to envelope, hydrophobic association with membrane and electrostatic attraction, have contributed to enhanced antibacterial photodynamic therapy of sophorolipid conjugated toluidine blue.
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